查看更多>>摘要：Lipoprotein lipase (LPL) deficiency is an extremely rare disorder of lipid metabolism known to cause hyper-triglyceridaemia in childhood. We report the incidental diagnosis of LPL deficiency in an infant presenting with an acute respiratory tract infection. The patient was initially treated for a lower respiratory tract infection, but was subsequently found to have milky appearance of the serum, with a triglyceride concentration greater than 1000 mg/dL. Clinical examination revealed hepatosplenomegaly. Genetic analysis showed that the patient was a compound heterozygote for two rare likely pathogenic LPL variants c.808C>G p.(Arg270Gly) and c.1019-3C >G. She was commenced on a low-fat diet with the addition of medium chain triglyceride formula. At follow-up, her serum triglyceride level was normal.
查看更多>>摘要：Background: NT-proBNP (N-terminal prohormone of brain natriuretic peptide) has been established as a useful biomarker in plasma for children with congenital heart disease (CHD). Plasma values were shown to correlate well with urinary values. We designed a study to investigate the general utility of urinary NT-proBNP in children with and without CHD in an ambulatory setting. Material and methods: 202 children (mean age 93 months (1-225 months)) were included in the analysis. We investigated the performance of urinary NT-proBNP values determined from spot urine as a diagnostic tool for different forms of congenital heart disease. Results: Urinary NT-proBNP is a good diagnostic tool for children with congenital heart disease (ROC area under the curve 0.807). Combining these values with the Ross-classification further improves the diagnostic power (ROC area under the curve 0.831) Analysis also showed significant differences between Lg(10) urinary NT-proBNP values of healthy controls and those of children after corrective surgery. Furthermore, children who have completed the stages of Fontan palliation showed higher values than age matched controls. Conclusions: Urinary NT-proBNP can be used in an ambulatory setting to discriminate between relevant and nonrelevant CHD and might be valuable as a follow up parameter for children after biventricular repair or univentricular palliation. Age dependant urinary NT-proBNP normal values for children could be an easy-to-use tool for general practitioners as well as specialised clinics.
查看更多>>摘要：Background: Thalassemia is a common inherited haemoglobin disorder worldwide, several methods have been utilized in the step-wise screening. Even though hundreds of mutations in globin genes have been reported, novel mutations are continuously emerging as the development of DNA sequencing. Methods: The case is a 27-year-old female with abnormal values of routine hematological indices, who was admitted for genetic screening of thalassemia. Genomic DNA was extracted and used for genetic assays cover 26 mutations in HBA and HBB genes: gap-PCR and agarose gel electrophoresis were performed to detect deletions, while PCR-reverse dot blot was used to detect point mutations. The next- and third- generation sequencing were used to identify the known and potential novel genotypes of thalassemia, and multiplex ligation-dependent probe amplification (MLPA) was used for genotype validation. Results: Hematological results indicate microcytic hypochmmic anemia, high HbA2 (7.2%) and high HbF (6.2%). None of the known genotypes of thalassemia were matched for this case, but a novel 4.9 Kb deletion at HBB gene (hg38, Chr11: 5226187-5231089) was discovered by the third-generation sequencing, the novel deletion was also validated by MLPA (8 probes, 11p15.4: 203314-207652). Conclusions: This study suggests the third-generation sequencing has promising potentiality to discover novel genotypes (especially deletions) of thalassemia.
查看更多>>摘要：Mesangial proliferative glomerulonephritis (MsPGN) is the most common clinicopathologic feature of the primary glomerulonephritis. The hereditary susceptibility to MsPGN is rather complex. In this report, a Chinese case of proliferative glomerulosclerosis was recruited. Renal biopsy revealed extensive glomerulosclerosis with mesangial hypertrophy, and tubular atrophy and dilatation. Whole exome sequencing (WES) revealed compound heterozygous variants in TTC21B gene, which were confirmed by Sanger sequencing. The variants in TTC21B gene were the molecular pathogenic basis of this disorder, and this case help to understand the correlation of genotype and phenotypes of TTC21B mutations.
Rao, Lokinendi, VPratt, George W.Bi, CaixiaKroll, Martin H....
4页
查看更多>>摘要：Introduction: HbA1c is a reliable biomarker for diagnosing and prognosis of diabetes, but many clinical scenarios and interfering factors can affect the test results. Any conditions that affect red cell turnover, such as iron-deficiency anemia (IDA), can lead to spurious HbA1c results. Reports on how IDA affects HbA1c concentrations are contradictory, and to understand better the association between HbA1c concentrations and IDA, we conducted a large-scale retrospective study. Methods: Test results for HbAlc concentrations were retrieved from the years 2015-2019. We evaluated over 12,000 patients with IDA and 21,000 patients without IDA. Patients were classified as having IDA if samples with below the age-based ranges for serum iron, ferritin, or transferrin iron saturation and above age-based ranges for transferrin iron-binding capacity or transferrin concentrations. Kruskal-Wallis statistical analyses method was used to test whether the two samples follow the same distribution and significance. Results: The median HbA1c concentration was 5.7% among IDA classified patients and 5.4% among normal samples (P < 0.001) for females. For males, the median HbA1c concentration was 6.0% among IDA classified patients and 5.6% among normal samples (P < 0.001). Conclusion: Patients classified as IDA can have increased HbA1c concentrations than patients without IDA. Clinicians should consider IDA status before making therapeutic decisions based on HbA1c concentrations.
查看更多>>摘要：Background and aims: Incomplete surgical resection of invasive non-functional pituitary adenomas (NFPAs) produces a risk of the subsequent development of complications which will require treatment with powerful drugs and adjuvant radiotherapy. Materials and methods: The degree of invasiveness of NFPA can be established using biomarkers to help clinicians choose appropriate treatment for these patients. Results: This research explored transcriptomic and proteomic variations of non-invasive and invasive NFPAs, other forms of pituitary adenomas and evaluated exosomal genetic markers associated with these diseases. Increased expression of matrix metalloproteinase-1 (MMP1) and its formation in exosomes (exo-MMP1) were correlated with the characteristic invasiveness of NFPAs. Changes in the expression of MMP1 in the exosome was synchronized with transduction of NFPA cells. Enrichment of MMP1 stimulated migration, growth and angiogenesis in tumors through the protease-activated receptor-1 signaling pathway in cells. Conclusion: The results revealed that MMP1 activity has obligatory actions in promoting tumor invasion and angiogenesis, and that the exosome-mediated regulatory pathway for MMP1 may be a novel therapeutic target.
查看更多>>摘要：Accumulation of reactive oxygen species (ROS) can induce both protein tyrosine nitration and endothelial dysfunction in atherosclerosis. Endothelial dysfunction refers to impaired endothelium-dependent vasorelaxation that can be triggered by an imbalance in nitric oxide (NO) production and consumption. ROS reacts with NO to generate peroxynitrite, decreasing NO bioavailability. Peroxynitrite also promotes protein tyrosine nitration in vivo that can affect protein structure and function and further damage endothelial function. In this review, we discuss the process of protein tyrosine nitration, increased expression of nitrated proteins in cardiovascular disease and their association with endothelial dysfunction, and the interference of tyrosine nitration with antioxidants and the protective role in endothelial dysfunction. These may lead us to the conception that protein tyrosine nitration may be one of the causes of endothelial dysfunction, and help us gain information about the mechanism of endothelial dysfunction underlying atherosclerosis.
查看更多>>摘要：Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human pathogen causing coronavirus disease 2019 (COVID-19). Rare cases of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) after the ChAdOx1 nCoV-19 (AstraZeneca) vaccination have been reported. We performed a test for anti-heparin/platelet factor 4 (PF4) antibodies and functional assay using flow cytometry. Method: A healthy woman presented to the emergency department with chest pain, headache, and abdominal pain after the first vaccination with AstraZeneca. Polymerase chain reaction (PCR) test for SARS-CoV-2 was negative. Chest computed tomography (CT) showed pulmonary artery embolism and brain magnetic resonance imaging (MRI) revealed cerebral sinus-venous thrombosis. Abdominal CT demonstrated the thrombosis with occlusion in her right hepatic vein. Laboratory studies revealed decreased platelet counts, and high D-dimer level. Finally, laboratory results indicated high PF4 antibodies level high and a positive platelet activation test, confirming the diagnosis of VITT. Results: Treatments including intravenous immunoglobulin, methylprednisolone and direct oral anticoagulant were administered. The results of a follow-up platelet count and D-dimer were normal. In addition, the titer of PF4 antibodies (optical density: 0.425; normal <= 0.4, enzyme-linked immunosorbent assay) fell. After a 3-month follow-up, her general condition improved gradually. Conclusions: The use of COVID-19 vaccines to prevent SARS-CoV-2 infections and complications is considered the most practicable policy for controlling the COVID-19 pandemic and is being forcefully pursued in the global area. Appropriate laboratory diagnosis facilitates the accurate and rapid diagnosis. Early recognizing and appropriate strategies for VITT are required and can provide these patients with more favorable patient outcomes. This report also elected to make comparisons of clinical manifestation, laboratory diagnosis, and management in patients with VITT.
查看更多>>摘要：Copeptin, a glycosylated peptide of 39 amino acids, is the C-terminal segment of arginine vasopressin (AVP) precursor peptide, which is consisted of two other fragments, vasopressin and neurophysin II. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis and regulation of the endocrine stress response. Numerous studies have demonstrated that the endogenous AVP in plasma is a meaningful biomarker to guide diagnosis and therapy of diseases associated with fluids disorders and stress. However, due to its instability, short half-time life in circulation and lack of readily available AVP assays, clinical measurement of AVP is restricted. In contrast to AVP, copeptin which is released in an equimolar mode with AVP from the pituitary, has emerged as a stable and simple-to-measure surrogate marker of AVP and displays excellent potential in diagnosis, differentiation and prognosis of various diseases. This review will discuss the studies on the clinical value of copeptin in different diseases, especially in AVP-dependent fluids disorders, as well as issues and prospects of the application of this potential biomarker.
Gok, VeyselTada, HayatoDogan, Muhammet EnsarSari, Ummu Alakus...
6页
查看更多>>摘要：Background: Sitostemlemia, also known as phytosterolemia, results from increased intestinal absorption of plant sterols and decreased intestinal and biliary excretion of sterols, resulting in increased levels of plant sterols in the plasma. The most common symptoms include xanthomas, premature atherosclerosis, hemolytic anemia and macrothrombocytopenia, however delayed diagnosis or misdiagnosis also occur. Patient and methods: Clinical exome sequencing was performed on a 10-year-old boy whom we followed up with signs of pancytopenia accompanied by macrothrombocytopenia and stomatocytosis. In addition, the blood sterol levels of the patient and his family were studied. Results: A novel homozygous c.904 + 5G > C intmnic variant was detected in ABCG5 gene in index case. The mother and father were identified as carriers. The blood plant sterol levels of the patient and his family were studied, and the levels in the patient confirmed Sitosterolemia. Sitosterol levels decreased dramatically with restricted diet and ezetimibe treatment. Conclusion: In children, signs of Sitosterolemia may be subtle and the only symptom may be hematological. Therefore, Sitosterolemia should be kept in mind in children with stomatocytosis and macrothrombocytopenia.
NSTL
Elsevier